MicroRNA trimming in the nervous system

Abstract

MicroRNAs are small, single-stranded RNAs about 22 nucleotides long which are involved in post-transcriptional regulation of mRNAs. MicroRNAs base-pair with regions on the 3’ UTR of target mRNAs which show partial complementarity to microRNA sequence and downregulate them by translational repression or mRNA cleavage. To effect their biological functions, microRNAs require loading into the RNA-induced silencing complex by the Argonaute protein, the catalytic subunit of RISC. There are four proteins in the Argonaute protein family: Ago1, Ago2, Ago3 and Ago4. Ago2 mediates mRNA cleavage upon perfect sequence complementarity between mRNA and microRNA, whereas Ago1, 3 and 4 cause translational repression. MicroRNA-124 is a microRNA which regulates neuronal differentiation and is expressed in immature and terminally-differentiated neurons. It occurs as a population of 20-25 nucleotide-long microRNAs in the mouse brain. Upon maturation of the nervous system, the miR-124 population slowly changes from 22-mer as the most abundant form to 21-mer as the most abundant form, a process called microRNA trimming. [1st Award]